A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a ....A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a role in the development of diabetes in humans. In plants, sugars affect many processes including growth, flowering, photosynthesis, nitrogen metabolism, starch synthesis, pigmentation and response to pathogens.Read moreRead less
Plasmid maintenance and interactions with the host cell and its genome. Plasmids are extrachromosomal genetic elements that play a central role in the evolution of bacteria. They are the most dynamic component of the bacterial genome, augmenting the host chromosome by conferring a range of significant phenotypes that facilitate environmental adaptation. This project aims to elucidate fundamental aspects of the relationship between plasmids and their bacterial hosts. Significant outcomes include ....Plasmid maintenance and interactions with the host cell and its genome. Plasmids are extrachromosomal genetic elements that play a central role in the evolution of bacteria. They are the most dynamic component of the bacterial genome, augmenting the host chromosome by conferring a range of significant phenotypes that facilitate environmental adaptation. This project aims to elucidate fundamental aspects of the relationship between plasmids and their bacterial hosts. Significant outcomes include understanding the molecular basis of efficient plasmid inheritance in bacterial populations, and exploration of the innovative hypothesis that plasmids modulate expression of the host chromosome, a possibility that would profoundly alter our view of how plasmids influence host phenotype.Read moreRead less
Identifying Novel Biosynthetic Pathways in Mycobacteria using DNA Microarray Technology. DNA microarrays are a powerful new bioinformatics-based technology and an ideal tool for characterising complex biosynthetic pathways since the expression of all genes in the bacterial genome can be monitored in a single experiment. In this project we aim to construct and use a DNA microarray to identify novel biosynthetic pathways in mycobacteria. Of particular interest are pathways used to create compone ....Identifying Novel Biosynthetic Pathways in Mycobacteria using DNA Microarray Technology. DNA microarrays are a powerful new bioinformatics-based technology and an ideal tool for characterising complex biosynthetic pathways since the expression of all genes in the bacterial genome can be monitored in a single experiment. In this project we aim to construct and use a DNA microarray to identify novel biosynthetic pathways in mycobacteria. Of particular interest are pathways used to create components of the highly complex and poorly characterised cell wall. Since this structure is unique in the bacterial world, we expect to identify and characterise pathways that are unique to mycobacteria.Read moreRead less
The evolution of bacterial pathogenesis: a genomic approach. The outcome of this research will be a better understanding of the genes involved with adaptation to particular pathogenic lifestyles. Specifically, genes that are rapidly evolving in selected bacterial pathogens of medical and veterinary importance will be identified using a bioinformatics approach that exploits the existence of multiple closely-related genome sequences. Such genes encode potential new targets for therapeutic interv ....The evolution of bacterial pathogenesis: a genomic approach. The outcome of this research will be a better understanding of the genes involved with adaptation to particular pathogenic lifestyles. Specifically, genes that are rapidly evolving in selected bacterial pathogens of medical and veterinary importance will be identified using a bioinformatics approach that exploits the existence of multiple closely-related genome sequences. Such genes encode potential new targets for therapeutic intervention that provide alternatives in the face of emerging antibiotic resistance. Importantly, the methodology developed in this project is broadly applicable to the study of evolution of bacterial pathogenesis in any background: medical, agricultural or horticultural.Read moreRead less
Transcriptional control of antigenic variation in the malaria parasite Plasmodium falciparum. Malaria is a major health concern for the Australian Defence Personnel recently deployed in East Timor, Afghanistan and the Solomon Islands and is endemic in our immediate neighbours Indonesia and Papua New Guinea. Australia is susceptible to malaria and climate change could extend the mosquitos range to large population centres of Northern Australia causing malaria in Australia. This study would clarif ....Transcriptional control of antigenic variation in the malaria parasite Plasmodium falciparum. Malaria is a major health concern for the Australian Defence Personnel recently deployed in East Timor, Afghanistan and the Solomon Islands and is endemic in our immediate neighbours Indonesia and Papua New Guinea. Australia is susceptible to malaria and climate change could extend the mosquitos range to large population centres of Northern Australia causing malaria in Australia. This study would clarify how malaria parasites evade the host's immune response and help to protect Australia by providing drug targets for the control of this invasive disease.Read moreRead less
Structural analysis and functional inactivation of bacterial transcription complexes. RNA polymerase is an essential enzyme in all living cells. Its role is to convert the genetic information stored in genes into a message that can be converted into protein. As such, the bacterial RNA polymerase represents an ideal target for the development of new antibiotics which will be important in maintaining the health of the Australian community and also in protecting the community from the very real thr ....Structural analysis and functional inactivation of bacterial transcription complexes. RNA polymerase is an essential enzyme in all living cells. Its role is to convert the genetic information stored in genes into a message that can be converted into protein. As such, the bacterial RNA polymerase represents an ideal target for the development of new antibiotics which will be important in maintaining the health of the Australian community and also in protecting the community from the very real threat of bioterrorism organisms such as anthrax. This project is designed to identify molecules for development as new antibiotics that are effective against RNA polymerase.Read moreRead less
Sulfur cycling in soil environments - how bacteria contribute to the oxidation of organic and inorganic sulfur compounds. Element cycling in soil environments is of global significance as soils constantly exchange compounds with the atmosphere and cover vast areas of land. Many of the compounds exchanged are known contributors to the greenhouse effect and other phenomena such as acid rain. By elucidating the regulation of bacterial sulfur oxidation pathways and their integration into general met ....Sulfur cycling in soil environments - how bacteria contribute to the oxidation of organic and inorganic sulfur compounds. Element cycling in soil environments is of global significance as soils constantly exchange compounds with the atmosphere and cover vast areas of land. Many of the compounds exchanged are known contributors to the greenhouse effect and other phenomena such as acid rain. By elucidating the regulation of bacterial sulfur oxidation pathways and their integration into general metabolism, we will enable the development of better management strategies for agricultural soils. Our data will also significantly improve understanding of how soil processes will change in response to changing climatic conditions.Read moreRead less
Understanding an exotic disease: Initiation of sex and infection by the sugarcane smut Ustilago scitaminea. Australian sugar exports generate almost $2 billion in annual sales, making the sugar industry a critical facet of the Australian economy. In 2006, Australia's primary sugar producing region came under threat when an outbreak of sugarcane smut caused by the fungus Ustilago scitaminea first appeared in Queensland. Management of this potentially devastating disease has focused on breeding pr ....Understanding an exotic disease: Initiation of sex and infection by the sugarcane smut Ustilago scitaminea. Australian sugar exports generate almost $2 billion in annual sales, making the sugar industry a critical facet of the Australian economy. In 2006, Australia's primary sugar producing region came under threat when an outbreak of sugarcane smut caused by the fungus Ustilago scitaminea first appeared in Queensland. Management of this potentially devastating disease has focused on breeding programmes aimed at developing resistant sugarcane cultivars, a complex process hampered by a lack of information about the mechanisms of smut resistance. Our research will provide key insight into the mechanisms by which U. scitaminea infects sugarcane, directing future breeding efforts and protecting this valuable industry against further outbreaks.Read moreRead less
Decoding regulatory RNA function in bacteria. All complex biological processes in bacterial cells appear to utilise regulatory small RNAs to control gene expression, but we lack a systems-level understanding of their functions and mechanisms of control. This proposal aims to address this fundamental knowledge gap using machine learning and cutting-edge, systems-level techniques to determine how small RNA sequence and structure determines function. Small RNAs have been found to control a broad ra ....Decoding regulatory RNA function in bacteria. All complex biological processes in bacterial cells appear to utilise regulatory small RNAs to control gene expression, but we lack a systems-level understanding of their functions and mechanisms of control. This proposal aims to address this fundamental knowledge gap using machine learning and cutting-edge, systems-level techniques to determine how small RNA sequence and structure determines function. Small RNAs have been found to control a broad range of traits including metabolism, biofilm formation, antibiotic tolerance, and virulence. The work proposed here will enhance our ability to predict and control bacterial gene expression with potential future impacts on bioproduction, synthetic biology, and veterinary and medical microbiology.Read moreRead less
Investigations into the antibacterial mechanism of action of cannabidiol. Cannabidiol (CBD) comes from a set of naturally occurring compounds, with a range of applications in mainstream culture. We have recently reported that CBD has excellent antimicrobial properties, with the ability to kill bacteria. This project aims to understand how CBD works by examining CBD-bacterial interactions at a genetic and molecular level. By understanding how CBD acts on and within bacterial cells, we can create ....Investigations into the antibacterial mechanism of action of cannabidiol. Cannabidiol (CBD) comes from a set of naturally occurring compounds, with a range of applications in mainstream culture. We have recently reported that CBD has excellent antimicrobial properties, with the ability to kill bacteria. This project aims to understand how CBD works by examining CBD-bacterial interactions at a genetic and molecular level. By understanding how CBD acts on and within bacterial cells, we can create fundamental new knowledge that could lead to the design of improved analogs of CBD to that can treat bacterial infections. As a much-needed completely new antibiotic class, this will lead to significant benefits, supporting Australia's National Strategy to combat the challenges posed by antimicrobial resistance.Read moreRead less